Gene therapy progress and prospects: Parkinson's disease

PD is an attractive target for central nervous system (CNS) gene therapy for several reasons. First, the pathology in early PD is, to a first approximation, limited to dopaminergic neurons projecting from the substantia nigra pars compacta (SNc) to the caudate aputamenl, so that localized gene delivery is a viable therapeutic strategy. Second, the neurochemical deficits and the functional consequences of dopaminergic cell loss on local basal ganglia circuitry are well characterized; gene transfer can be designed either to improve cell survival, or to modify functional activity in the damaged basal ganglia circuitry. Third, PD is common and disabling despite treatment; no current intervention is uniformly accepted as altering the natural history of disease progression; hence, development of novel therapeutics is desirable. A variety of therapeutic transgenes has been delivered in experimental models of PD, using a number of different vectors. In this article, we survey the literature from 2000 to 2003, and briefly review recent progress in the development of gene transfer strategies for treating PD.